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• W4205635522 abstract "The rich source of graduate students, keen to get their PhDs, was a big plus at Wisconsin. My plan was to address numerous issues sequentially: the development of acquired resistance to tamoxifen following years of treatment in athymic mice, investigate the metabolites of tamoxifen in athymic mice and human serum samples from UWCCC serum bank, and investigate the pharmacology of a failed breast cancer antiestrogen keoxifene (that became raloxifene half a decade later with a name change!). The studies of the unanticipated switching on (bone, lowering cholesterol) and off (breast cancer) gave the world selective estrogen receptor modulators. To investigate the role of growth factors in tamoxifen resistance and conduct extensive studies of the structure–activity relationships of nonsteroidal estrogens and antiestrogens in vitro, investigate ER replication and recycling in breast cancer cells, become the first group to stably transfect the ER gene into ER-negative breast cancer cells and discovered the estrogen-like properties of 19-nortestosterone. However, the investigation that the critical amino acid Asp351 was mutated to tyrosine in a tamoxifen-dependent MCF-7 cell line created an opportunity to investigate the molecular pharmacology of Asp351 was not of interest to the academic community. Now it is known as the critical amino acid and the key to the antiestrogenic side chain of antiestrogens acting as a “stick in the jaws of the crocodile,” and Asp351 is the anchor that seals and activates the ER with mutations in helix 12 that occur during aromatase inhibitor therapy. However, Marco Gottardis' discovery that tamoxifen prevents the growth of breast cancer, but tamoxifen causes endometial cancer to grow, changed clinical practice and lives were saved." @default.
• W4205635522 created "2022-01-26" @default.
• W4205635522 creator A5049919852 @default.
• W4205635522 date "2022-01-01" @default.
• W4205635522 modified "2023-09-23" @default.
• W4205635522 title "The good, the bad and the ugly of tamoxifen at Wisconsin" @default.
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• W4205635522 doi "https://doi.org/10.1016/b978-0-323-85051-3.00008-7" @default.
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